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Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.

Xu L, Peng Q, Xuan W, Feng X, Kong X, Zhang M, Tan W, Xue M, Wang F - Mediators Inflamm. (2016)

Bottom Line: The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA.Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium.Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

ABSTRACT
We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.

No MeSH data available.


Related in: MedlinePlus

IL-29-induced cytokine expression by OA synovial fibroblasts. mRNA levels of IL-1β (a), IL-6 (b), IL-8 (c), and MMP-3 (d) in OA FLS after exposure to IL-29 (1, 10, and 100 ng/mL) with or without its blocking antibody for 48 h were determined by real-time PCR. The results shown are representative of one of three independent experiments. The error bars represent mean ± SEM for triplicate wells. ∗P < 0.05 versus medium control. #P < 0.05 versus IL-29 (100 ng/mL) treatment group.
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fig4: IL-29-induced cytokine expression by OA synovial fibroblasts. mRNA levels of IL-1β (a), IL-6 (b), IL-8 (c), and MMP-3 (d) in OA FLS after exposure to IL-29 (1, 10, and 100 ng/mL) with or without its blocking antibody for 48 h were determined by real-time PCR. The results shown are representative of one of three independent experiments. The error bars represent mean ± SEM for triplicate wells. ∗P < 0.05 versus medium control. #P < 0.05 versus IL-29 (100 ng/mL) treatment group.

Mentions: As shown in Figure 4, IL-29 induced a dose-dependent upregulation of IL-1β, IL-6, IL-8, and MMP-3 mRNA in OA FLS following 48 h incubation. Furthermore, the action of IL-29 on these cytokine expressions in OA FLS was abolished by addition of IL-29 blocking antibody at the concentration of 2000 and 3000 ng/mL. These data indicate that IL-29 stimulates proinflammatory cytokine expression on OA FLS.


Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.

Xu L, Peng Q, Xuan W, Feng X, Kong X, Zhang M, Tan W, Xue M, Wang F - Mediators Inflamm. (2016)

IL-29-induced cytokine expression by OA synovial fibroblasts. mRNA levels of IL-1β (a), IL-6 (b), IL-8 (c), and MMP-3 (d) in OA FLS after exposure to IL-29 (1, 10, and 100 ng/mL) with or without its blocking antibody for 48 h were determined by real-time PCR. The results shown are representative of one of three independent experiments. The error bars represent mean ± SEM for triplicate wells. ∗P < 0.05 versus medium control. #P < 0.05 versus IL-29 (100 ng/mL) treatment group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940582&req=5

fig4: IL-29-induced cytokine expression by OA synovial fibroblasts. mRNA levels of IL-1β (a), IL-6 (b), IL-8 (c), and MMP-3 (d) in OA FLS after exposure to IL-29 (1, 10, and 100 ng/mL) with or without its blocking antibody for 48 h were determined by real-time PCR. The results shown are representative of one of three independent experiments. The error bars represent mean ± SEM for triplicate wells. ∗P < 0.05 versus medium control. #P < 0.05 versus IL-29 (100 ng/mL) treatment group.
Mentions: As shown in Figure 4, IL-29 induced a dose-dependent upregulation of IL-1β, IL-6, IL-8, and MMP-3 mRNA in OA FLS following 48 h incubation. Furthermore, the action of IL-29 on these cytokine expressions in OA FLS was abolished by addition of IL-29 blocking antibody at the concentration of 2000 and 3000 ng/mL. These data indicate that IL-29 stimulates proinflammatory cytokine expression on OA FLS.

Bottom Line: The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA.Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium.Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

ABSTRACT
We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.

No MeSH data available.


Related in: MedlinePlus